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Ankilozan Spondilit Ön Tanılı Hastalarda HLA-B27 Sıklığı

Yıl 2021, Cilt: 12 Sayı: 3, 364 - 370, 25.12.2021
https://doi.org/10.22312/sdusbed.963009

Öz

Amaç: Ankilozan spondilitin (AS) oluşumunda genetik faktörlerin önemli olduğu kabul edilmiştir. Hastalığın patogenezinde rol alan en önemli genetik faktörlerden birinin insan lökosit antijen (HLA)-B27 olduğu bilinmektedir. Bu çalışmada AS ön tanılı hastalarda HLA-B27 sıklığının tespit edilmesi ve hastaların demografik ve laboratuvar bulguları ile HLA-B27 arasındaki ilişkinin karşılaştırılması amaçlandı.

Materyal-Metod: AS ön tanılı 64’ü erkek, 91’i kadın olmak üzere toplam 155 hasta çalışmaya dahil edildi. Hastaların poliklinik takip dosyaları geriye dönük taranarak demografik özellikleri, genetik soyağacı bilgileri, laboratuvar bulguları ve HLA-B27 gen analizi sonuçları kaydedildi. Hastaların HLA-B27 analizleri Real-Time PCR yöntemi ile yapıldı.

Bulgular: Elde edilen bulgulara göre çalışmaya alınan AS ön tanılı hastaların 31’inde (%20) HLA-B27’nin pozitif olduğu saptandı. Erkeklerde HLA-B27 pozitifliği daha yüksekti (p=0,010). Yaş ortalaması cinsiyetler arasında fark göstermedi (p>0,05). HLA-B27 pozitif olanların yaş ortalaması negatif olanlara kıyasla anlamlı derecede düşüktü (p=0,047). Serum CRP ve sedimentasyon seviyeleri HLA-B27 pozitifliğinde belirleyici değildi (p>0,05). HLA-B27 pozitif olan hastalarda aile öyküsü olanlar olmayanlara kıyasla daha fazlaydı (p=0,000).

Sonuç: AS semptomlarını taşıyan hastalarda HLA-B27 pozitiflik oranı literatürden farklı olarak düşük bulundu. Bu farklılığın, AS ön tanılı hastaların çalışmaya dahil edilmesi, farklı hasta popülasyonu, klinik varyasyonlar, farklı etnik köken ve farklı genetik ve/veya çevresel faktörlerden kaynaklanmış olabileceğini düşünmekteyiz. Toplumumuzda AS hastalarında HLA-B27 frekansını daha net ortaya koyabilmek için kesin tanı almış daha geniş hasta popülasyonunda çalışmalara ihtiyaç vardır. 

Kaynakça

  • [1] Brown MA. Progress in the genetics of ankylosing spondylitis. Brief Funct Genomics 2011;10(5):249–57.
  • [2] Dakwar E, Reddy J, Vale FL, Uribe JS. A review of the pathogenesis of ankylosing spondylitis. Neurosurg Focus 2008;24(1):E2.
  • [3] Dean LE, Jones GT, Macdonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatol (United Kingdom) 2014;53(4):650–7.
  • [4] Diyarbakır E. The Distribution of HLA B27 in Patients with Ankylosing Spondylitis in Eastern Anatolia. J Inonu Univ Med Fac 2012;19(1):23–5.
  • [5] Chen B, Li J, He C, Li D, Tong W, Zou Y, et al. Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review). Mol Med Rep 2017;15(4):1943–51.
  • [6] Pekacar FS, Akdoğan A, Hayran M, Çolak R, Yılmaz E. Ankilozan spondilit ile HLA-B27, MEFV gen mutasyonları, ERAP1, IL12B ve IL23R gen polimorfizmleri arasındaki ilişki. Turkish J Biochem 2014;39(4):482–7.
  • [7] Yang T, Duan Z, Wu S, Liu S, Zeng Z, Li G, et al. Association of HLA-B27 genetic polymorphisms with ankylosing spondylitis susceptibility worldwide: A meta-analysis. Mod Rheumatol 2014;24(1):150–61.
  • [8] Gunal EK, Sarvan FO, Kamali S, Gul A, Inanc M, Carin M, et al. Low frequency of HLA-B27 in ankylosing spondylitis patients from Turkey. Jt Bone Spine 2008;75(3):299–302.
  • [9] Pedersen SJ, Maksymowych WP. The Pathogenesis of Ankylosing Spondylitis: an Update . Curr Rheumatol Rep 2019;21(10):58.
  • [10] Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, Shatford JL, et al. Susceptibility to ankylosing spondylitis in twins: The role of genes, HLA, and the environment. Arthritis Rheum 1997;40(10):1823–8.
  • [11] Cipriani A, Rivera S, Hassanhi M, Márquez G, Hernández R, Villalobos C, et al. HLA-B27 subtypes determination in patients with ankylosing spondylitis from Zulia, Venezuela. Hum Immunol 2003;64(7):745–9.
  • [12] Feldtkeller E, Khan MA, Van Der Heijde D, Van Der Linden S, Braun J. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int 2003;23(2):61–6.
  • [13] Wu Z, Lin Z, Wei Q, Gu J. Clinical features of ankylosing spondylitis may correlate with HLA-B27 polymorphism. Rheumatol Int 2009;29(4):389–92.
  • [14] Khan MA, Kushner I, Braun WE. Comparison of clinical features in HLA‐B27 positive and negative patients with ankylosing spondylitis. Arthritis Rheum 1977;20(4):909–12.
  • 15] Mekhola MH, Chowdhury MAJ, Ahmed MS, Khan AH, Paul S. Frequency of HLA-B27 gene among patients with ankylosing spondylitis and its consequences on clinical manifestation. BIRDEM Med J 2019;9(3):188–92.
  • [16] Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing spondylitis: An overview. Ann Rheum Dis 2002;61 Suppl 3(Suppl 3):iii8-18.
  • [17] Arévalo M, Gratacós Masmitjà J, Moreno M, Calvet J, Orellana C, Ruiz D, et al. Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: Results from the REGISPONSER database. Arthritis Res Ther 2018;20(1).
  • [18] Akkoç N, Yarkan H, Kenar G, Khan MA. Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease. Curr Rheumatol Rep 2017 May;19(5):26.
  • [19] Ez-Zaitouni Z, Hilkens A, Gossec L, Berg IJ, Landewé R, Ramonda R, et al. Is the current ASAS expert definition of a positive family history useful in identifying axial spondyloarthritis? Results from the SPACE and DESIR cohorts. Arthritis Res Ther 2017;19(1).
  • [20] van Lunteren M, Sepriano A, Landewé R, Sieper J, Rudwaleit M, van der Heijde D, et al. Do ethnicity, degree of family relationship, and the spondyloarthritis subtype in affected relatives influence the association between a positive family history for spondyloarthritis and HLA-B27 carriership? Results from the worldwide ASAS cohort. Arthritis Res Ther 2018;20(1).

Frequency of HLA-B27 in Patients with Pre-Diagnosis of Ankylosing Spondylitis

Yıl 2021, Cilt: 12 Sayı: 3, 364 - 370, 25.12.2021
https://doi.org/10.22312/sdusbed.963009

Öz

Objectives: Genetic factors have been acknowledged as crucial in ankylosing spondylitis (AS) genesis. Human leukocyte antigen (HLA)-B27 known to play a role in the pathogenesis of the disease. In this study, it was aimed to determine the frequency of HLA-B27 in patients with pre-diagnosis of AS and to compare the relationship between demographic and laboratory findings and HLA-B27.

Material-Method: A total of 155 patients, 64 male and 91 female, with pre-diagnosis of AS were included in the study. Demographic characteristics, pedigree information, laboratory findings and HLA-B27 gene analysis results were recorded from the policlinic files of the patients. HLA-B27 analyzes were performed by Real-Time PCR method.

Results: HLA-B27 positivity was detected in 31 (20%) of AS patients. HLA-B27 positivity was higher in men (p=0.010). The mean age did not differ between the genders (p>0.05). The mean age of those who were HLA-B27 positive was significantly lower than those who were negative (p=0.047). Serum CRP and sedimentation levels were not determinative in HLA-B27 positivity (p>0.05). It was more common in HLA-B27 positive patients than those without family history (p=0.000).

Conclusion: The HLA-B27 positivity rate was found to be low in patients with AS symptoms. We suggest that this difference may be due to the inclusion of patients with pre-diagnosis of AS, different patient population, clinical variations, different ethnic origin and different genetic and/or environmental factors. In order to more clearly reveal the HLA-B27 frequency in AS patients, studies with a larger patient population are needed.

Kaynakça

  • [1] Brown MA. Progress in the genetics of ankylosing spondylitis. Brief Funct Genomics 2011;10(5):249–57.
  • [2] Dakwar E, Reddy J, Vale FL, Uribe JS. A review of the pathogenesis of ankylosing spondylitis. Neurosurg Focus 2008;24(1):E2.
  • [3] Dean LE, Jones GT, Macdonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatol (United Kingdom) 2014;53(4):650–7.
  • [4] Diyarbakır E. The Distribution of HLA B27 in Patients with Ankylosing Spondylitis in Eastern Anatolia. J Inonu Univ Med Fac 2012;19(1):23–5.
  • [5] Chen B, Li J, He C, Li D, Tong W, Zou Y, et al. Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review). Mol Med Rep 2017;15(4):1943–51.
  • [6] Pekacar FS, Akdoğan A, Hayran M, Çolak R, Yılmaz E. Ankilozan spondilit ile HLA-B27, MEFV gen mutasyonları, ERAP1, IL12B ve IL23R gen polimorfizmleri arasındaki ilişki. Turkish J Biochem 2014;39(4):482–7.
  • [7] Yang T, Duan Z, Wu S, Liu S, Zeng Z, Li G, et al. Association of HLA-B27 genetic polymorphisms with ankylosing spondylitis susceptibility worldwide: A meta-analysis. Mod Rheumatol 2014;24(1):150–61.
  • [8] Gunal EK, Sarvan FO, Kamali S, Gul A, Inanc M, Carin M, et al. Low frequency of HLA-B27 in ankylosing spondylitis patients from Turkey. Jt Bone Spine 2008;75(3):299–302.
  • [9] Pedersen SJ, Maksymowych WP. The Pathogenesis of Ankylosing Spondylitis: an Update . Curr Rheumatol Rep 2019;21(10):58.
  • [10] Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, Shatford JL, et al. Susceptibility to ankylosing spondylitis in twins: The role of genes, HLA, and the environment. Arthritis Rheum 1997;40(10):1823–8.
  • [11] Cipriani A, Rivera S, Hassanhi M, Márquez G, Hernández R, Villalobos C, et al. HLA-B27 subtypes determination in patients with ankylosing spondylitis from Zulia, Venezuela. Hum Immunol 2003;64(7):745–9.
  • [12] Feldtkeller E, Khan MA, Van Der Heijde D, Van Der Linden S, Braun J. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int 2003;23(2):61–6.
  • [13] Wu Z, Lin Z, Wei Q, Gu J. Clinical features of ankylosing spondylitis may correlate with HLA-B27 polymorphism. Rheumatol Int 2009;29(4):389–92.
  • [14] Khan MA, Kushner I, Braun WE. Comparison of clinical features in HLA‐B27 positive and negative patients with ankylosing spondylitis. Arthritis Rheum 1977;20(4):909–12.
  • 15] Mekhola MH, Chowdhury MAJ, Ahmed MS, Khan AH, Paul S. Frequency of HLA-B27 gene among patients with ankylosing spondylitis and its consequences on clinical manifestation. BIRDEM Med J 2019;9(3):188–92.
  • [16] Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing spondylitis: An overview. Ann Rheum Dis 2002;61 Suppl 3(Suppl 3):iii8-18.
  • [17] Arévalo M, Gratacós Masmitjà J, Moreno M, Calvet J, Orellana C, Ruiz D, et al. Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: Results from the REGISPONSER database. Arthritis Res Ther 2018;20(1).
  • [18] Akkoç N, Yarkan H, Kenar G, Khan MA. Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease. Curr Rheumatol Rep 2017 May;19(5):26.
  • [19] Ez-Zaitouni Z, Hilkens A, Gossec L, Berg IJ, Landewé R, Ramonda R, et al. Is the current ASAS expert definition of a positive family history useful in identifying axial spondyloarthritis? Results from the SPACE and DESIR cohorts. Arthritis Res Ther 2017;19(1).
  • [20] van Lunteren M, Sepriano A, Landewé R, Sieper J, Rudwaleit M, van der Heijde D, et al. Do ethnicity, degree of family relationship, and the spondyloarthritis subtype in affected relatives influence the association between a positive family history for spondyloarthritis and HLA-B27 carriership? Results from the worldwide ASAS cohort. Arthritis Res Ther 2018;20(1).
Toplam 20 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Kuyaş Hekimler Öztürk 0000-0002-7075-8875

Halil Özbaş 0000-0002-7561-1450

Muhammet Yusuf Tepebaşı 0000-0002-1087-4874

Pınar Koşar 0000-0003-2602-5145

Yayımlanma Tarihi 25 Aralık 2021
Gönderilme Tarihi 6 Temmuz 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 12 Sayı: 3

Kaynak Göster

Vancouver Hekimler Öztürk K, Özbaş H, Tepebaşı MY, Koşar P. Ankilozan Spondilit Ön Tanılı Hastalarda HLA-B27 Sıklığı. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi. 2021;12(3):364-70.

SDÜ Sağlık Bilimleri Dergisi, makalenin gönderilmesi ve yayınlanması dahil olmak üzere hiçbir aşamada herhangi bir ücret talep etmemektedir. Dergimiz, bilimsel araştırmaları okuyucuya ücretsiz sunmanın bilginin küresel paylaşımını artıracağı ilkesini benimseyerek, içeriğine anında açık erişim sağlamaktadır.